FDA CRL - Celltrion Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Celltrion Inc. regarding its Biologics License Application (BLA 761338) for CT-P43, a proposed biosimilar. The application, submitted on June 30, 2023, could not be approved in its current form due to several product quality deficiencies.

Key issues identified primarily fall under product quality microbiology and general product quality. The FDA found the bacterial retention study for the 130 mg/26 mL single-dose vial inadequate and requires its repetition. Additionally, the container closure integrity test (CCIT) dye ingress method used for stability testing lacked validated reproducibility between different analysts, necessitating evidence of reproducibility or an alternative spectrophotometric method.

Furthermore, the proposed release and stability specifications for drug product clarity were deemed unacceptable, as they were not adequately justified by clinical and manufacturing experience. Celltrion is required to tighten these criteria based on historical long-term stability results. Similarly, the proposed shelf-life limit for another product component (unspecified due to redactions) across multiple presentations (45 mg/0.5 mL and 90 mg/mL PFS, and 130 mg/26 mL vial) was not supported by clinical or manufacturing data, requiring adjustment based on long-term stability.

The FDA reserved comments on prescribing information and carton/container labeling until these core deficiencies are resolved. The proprietary name, "Steqeyma," was conditionally acceptable but needs re-submission upon addressing all identified issues. Celltrion is also mandated to submit a comprehensive safety update, incorporating new nonclinical and clinical data, including a summary of worldwide safety experience.

This CRL indicates that Celltrion must address these significant quality and data justification issues before the application can be reconsidered for approval under section 351(k) of the Public Health Service Act.